Topical Diclofenac and Topical DFMO Chemoprevention Trial in Subjects With a History of Skin Cancer

Prior treatment

• Chronic (\> 3 times/week for more than a two week period) use of NSAIDs or COX-2 inhibitors
• Current use of topical steroids to intended treatment area (forearms)
• Use of oral or intravenous corticosteroids for more than 2 consecutive weeks
  • Any of the following in the 4 weeks prior to randomization:
• Major surgery for any indication
• Cytotoxic chemotherapy for any indication (including methotrexate for arthritis)
• Hormonal therapy for cancer prevention ((treatment with finasteride/dutasteride for BPH does not render a participant ineligible.)
• Radiation therapy
  • Any of the following in the 6 month prior to randomization to the intended treatment area (forearms):
• Solid organ or bone marrow transplant
• Oral DFMO for \> 1 month on a prior study
• An immunodeficiency disorder or the use of an immunosuppressive drug
  • Concurrent use of the following medications or treatments:
• Systemic therapy with psoralens, immunotherapy, or retinoids.
• Cytotoxic chemotherapy for any reason (including methotrexate for arthritis)
• Topical or systemic immunosuppressive therapy
  • Females who are pregnant or lactating. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should notify her study physician immediately.
  • Uncontrolled concurrent illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements or other underlying serious medical condition which, in the investigator's opinion might preclude study participation.

Other illness

• Anti-cancer treatment of any type other than for a stage 0-2 non-melanoma skin cancer
• Topical medications for the treatment of actinic keratosis or skin cancer (etretinate, 5-FU, imiquimod, ingenol)
• Laser resurfacing, dermabrasion, chemical peel and/or electrodissection ± curettage
  • Any family history of Ornithine diaminotransferase deficiency in a first degree relative
  • Any personal history of:
• Photosensitivity disorder
• Hypersensitivity or adverse reactions to nonsteroidal anti-inflammatory agents
• Any disease that predisposes to NMSC

Age

• Invasive cancer diagnosed or treated within the past 5 years. Participants who have been in remission for \>5 years and have not required treatment in the past 5 years may be eligible if a study chair or principal investigator believes there is little to no risk of recurrence.

Other

• Any of the following will render a participant ineligible to participate in this study:
• Aspirin \>100 mg/day
• Cryotherapy to intended treatment area (forearms) within the preceding 3 months
• Biopsy proven hepatic cirrhosis
• Keloid formation

• Previous treatment for basal or squamous cell skin cancer stage 0-2 and current evidence of at least actinic keratosis on the upper extremities (upper arms, forearms and hands), neck, face or scalp.
• \>18 years of age
• Ability to understand and willingness to sign a written informed consent document
• ECOG performance status 0-1
• Willing and able to participate for the full duration of the study
• Willing to abstain from:
  • The application of topical medications including prescription and over the counter preparations (e.g., Topical preparations containing corticosteroids or vitamin A derivatives) to intended treatment areas for the duration of the study. Use of moisturizers/emollients and sunscreens on these areas is allowed.
  • Chronic (defined as \> 3 times/week for more than 2 consecutive weeks/year) NSAID and COX-2 inhibitor use (other than cardioprotective doses of aspirin \< 100 mg po QD) for the duration of the study
• Normal organ and marrow function defined as laboratory values falling within the specified ranges for the following tests (performed within 365 days of registration)
  • Hematologic
• WBC \>3,000/ul
• Hemoglobin \> lower limit of normal
• Platelet count \> 100,000/ul
  • Hepatic
• Total bilirubin \< 1.5 X ULN
• AST (SGOT) \< 1.5 X ULN
• ALT (SPGT) \< 1.5 X ULN Renal
• Serum creatinine \< 1.5 X ULN BUN \< 1.5 X ULN
  • Females of childbearing potential must:
• Have been using adequate contraception (abstinence, IUD, birth control pills or spermicidal gel with diaphragm or condom) since their last menses
• Have a documented negative urine pregnancy test prior to the first dose of study medication. (Females are not considered to be of childbearing potential if they are at least 1 year post-menopausal or have had a tubal ligation, bilateral oophorectomy or hysterectomy)
• The effects of DFMO and diclofenac on the developing fetus are unknown. Therefore, all females of childbearing potential and all men capable of fathering a child must agree to use adequate contraception (abstinence, IUD, birth control pills, or spermicidal gel with diaphragm or condom) for the duration of study participation.